[2604.00580] Representation choice shapes the interpretation of protein conformational dynamics

Computer Science > Machine Learning arXiv:2604.00580 (cs) [Submitted on 1 Apr 2026] Title:Representation choice shapes the interpretation of protein conformational dynamics Authors:Axel Giottonini, Thomas Lemmin View a PDF of the paper titled Representation choice shapes the interpretation of protein conformational dynamics, by Axel Giottonini and 1 other authors View PDF HTML (experimental) Abstract:Molecular dynamics simulations provide detailed trajectories at the atomic level, but extracting interpretable and robust insights from these high-dimensional data remains challenging. In practice, analyses typically rely on a single representation. Here, we show that representation choice is not neutral: it fundamentally shapes the conformational organization, similarity relationships, and apparent transitions inferred from identical simulation data. To complement existing representations, we introduce Orientation features, a geometrically grounded, rotation-aware encoding of protein backbone. We compare it against common descriptions across three dynamical regimes: fast-folding proteins, large-scale domain motions, and protein-protein association. Across these systems, we find that different representations emphasize complementary aspects of conformational space, and that no single representation provides a complete picture of the underlying dynamics. To facilitate systematic comparison, we developed ManiProt, a library for efficient computation and analysis of multiple prot...